In recent years, we have conducted studies which involves the novel use of microdialysis in human skeletal muscle and adipose tissue. The technique involves the sampling of extracellular fluid (ECF) from body tissues allowing insights into local metabolic events. Preliminary studies were necessary to confirm feasibility and safety. Early observations determined that concentration gradients exist between ECF and intravascular compartments for substrates and high levels of glycerol (marker of lipolysis) seen in skeletal muscle indicated the presence of high rates of intramuscular lipolysis, a hitherto unrecognized metabolic phenomenon. Through the existence of the Randle cycle, we hypothesized that this metabolic process may locally impact muscle glucose metabolism in situ and bear relevance in insulin resistant states. Recent studies have indeed determined that regulation of intramuscluar lipolysis is abnormal in some insulin resistant states. We plan to study in more detail the role of intramuscular lipolysis in the insulin resistance of diabetes. In addition, recent success with laboratory and animal studies has confirmed the feasibility of sampling larger molecules (e.g. insulin, IGF-1 and leptin) in ECF and this development has raised the interesting possiblility of studying local peptide physiology as an adjunct to the metabolic studies already planned.